A program of research concerned with definition of the biochemical process of protein degradation in mammalian cardiac tissue and investigation of the cellular regulatory mechanisms controlling this process is presented. The regression phase of mechanically induced myocardial hypertrophy in a canine and rabbit preparation has been selected as a model for study. A broad based approach utilizing in vitro techniques with intact tissue preparations (the isolated rabbit right ventricular papillary muscle), broken cell preparations (subcellular fractions isolated by differential centrifugation) and purified enzyme preparations (cathepsin-D) isolated from heart tissue is outlined. Particular effort has been given to the development of improved methodology to allow for the investigation of specific problems not previously studied in mammalian myocardium.